Division of Reproductive Sciences, Department of Obstetrics & Gynecology, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado
J Appl Physiol (1985). 2017 Nov 1;123(5):1371-1385. doi: 10.1152/japplphysiol.00321.2017. Epub 2017 Aug 31.
High altitudes (>8,000 ft or 2,500 m) provide an experiment of nature for measuring adaptation and the physiological processes involved. Studies conducted over the past ~25 years in Andeans, Tibetans, and, less often, Ethiopians show varied but distinct O transport traits from those of acclimatized newcomers, providing indirect evidence for genetic adaptation to high altitude. Short-term (acclimatization, developmental) and long-term (genetic) responses to high altitude exhibit a temporal gradient such that, although all influence O content, the latter also improve O delivery and metabolism. Much has been learned concerning the underlying physiological processes, but additional studies are needed on the regulation of blood flow and O utilization. Direct evidence of genetic adaptation comes from single-nucleotide polymorphism (SNP)-based genome scans and whole genome sequencing studies that have identified gene regions acted upon by natural selection. Efforts have begun to understand the connections between the two with Andean studies on the genetic factors raising uterine blood flow, fetal growth, and susceptibility to Chronic Mountain Sickness and Tibetan studies on genes serving to lower hemoglobin and pulmonary arterial pressure. Critical for future studies will be the selection of phenotypes with demonstrable effects on reproductive success, the calculation of actual fitness costs, and greater inclusion of women among the subjects being studied. The well-characterized nature of the O transport system, the presence of multiple long-resident populations, and relevance for understanding hypoxic disorders in all persons underscore the importance of understanding how evolutionary adaptation to high altitude has occurred. Variation in O transport characteristics among Andean, Tibetan, and, when available, Ethiopian high-altitude residents supports the existence of genetic adaptations that improve the distribution of blood flow to vital organs and the efficiency of O utilization. Genome scans and whole genome sequencing studies implicate a broad range of gene regions. Future studies are needed using phenotypes of clear relevance for reproductive success for determining the mechanisms by which naturally selected genes are acting.
高海拔（>8000 英尺或 2500 米）提供了一个自然实验，用于测量适应和涉及的生理过程。过去 25 年来在安第斯人、藏人和埃塞俄比亚人中进行的研究显示了与适应高原的外来者不同但明显的 O 运输特征，为遗传适应高海拔提供了间接证据。对高海拔的短期（适应、发育）和长期（遗传）反应表现出时间梯度，尽管所有这些都影响 O 含量，但后者也改善了 O 的输送和代谢。我们已经了解了很多关于潜在生理过程的知识，但需要更多关于血流和 O 利用的调节的研究。遗传适应的直接证据来自基于单核苷酸多态性（SNP）的基因组扫描和全基因组测序研究，这些研究已经确定了自然选择作用的基因区域。已经开始努力了解安第斯山脉研究中提高子宫血流量、胎儿生长和对慢性高原病易感性的遗传因素以及藏人研究中降低血红蛋白和肺动脉压的基因之间的联系。未来研究的关键将是选择对生殖成功有明显影响的表型，计算实际的适应成本，并在研究对象中更多地包括女性。O 运输系统的特征明显，存在多个长期居住的人群，并且与理解所有人的低氧疾病有关，这些都突显了了解高海拔地区的进化适应是如何发生的重要性。安第斯山脉、藏人和埃塞俄比亚高原居民之间 O 运输特征的差异支持了改善向重要器官分配血流和提高 O 利用效率的遗传适应性的存在。基因组扫描和全基因组测序研究暗示了广泛的基因区域。未来需要使用与生殖成功明显相关的表型进行研究，以确定自然选择基因的作用机制。
